Genetic markers for predicting disease and treatment outcome

a gene and disease technology, applied in the field of pharmacogenomics, can solve the problems of inability to predict disease outcome, limited cancer chemotherapy, and inability to choose optimal therapy, and the mechanism by which tumor cells respond to radiation through these antiangiogenic/vascular agents is yet to be elucidated

Inactive Publication Date: 2006-06-01
UNIV OF SOUTHERN CALIFORNIA
View PDF26 Cites 50 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Cancer chemotherapy is limited by the predisposition of specific populations to drug toxicity or poor drug response.
Moreover, while adjuvant chemotherapy and radiation lead to a noticeable improvement in local control among those with rectal carcinoma, the choice of optimal therapy may be compromised by a wide inter-patient variability of tre

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

experimental examples

Example 1

Association of Polymorphism and Clinical Outcome of EGFR-Positive Cancer Patients Treated with Epidermal Growth Factor Receptor (EGFR) inhibitor, Cetuximab(C225)

[0156] This study identifies genomic polymorphisms of the EGFR pathway are useful as molecular markers to predict response to EGFR inhibitors, overall survival and toxicity. This study demonstrates that certain gene polymorphisms involved in the EGFR pathway, CyclinD1 (CCND1) A870G and EGF A61G, are associated with overall survival in metastatic CRC patients treated with the EGFR inhibitor cetuximab. When the analysis of Cyclin DI and EGF polymorphisms were combined together, patients with two favorable genotypes (EGF any A allele and CCND1 any G allele) showed a median survival time of 12 month (95% C.l 4.8-15.2), while patients with any unfavorable genotypes (EGF GG or CylinDI AA) survived only 4.4 months (95% C.l 2.1-5.7).(p=0.004, logrank test).

[0157] Patients

[0158] Thirty-nine patients with histopathologica...

example 2

Multi-Factorial Analysis of Metastatic Colorectal Cancer Patients Treated with Cetuximab

[0173] This study investigated whether mRNA expression levels of members of the EGFR signaling pathway, e.g., Cyclin D1 (CCNDI), cyclooxygenase 2 (COX-2), epidermal growth factor receptor (EGFR), Interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF), are associated with the clinical outcome in patients with EGFR-expressing metastatic colorectal cancer (CRC) treated with cetuximab.

Patients

[0174] The same patient sample of Experimental Example 2 was used for this study.

Sample Preparation

[0175] For the evaluation of gene expression levels, tumor samples were obtained from the primary colorectal tumor or from metastatic site of the liver at the time of diagnosis. Paraffin-embedded tumor blocks were reviewed for quality and tumor content by a pathologist. Ten (10) micrometer thick sections were obtained from the identified areas with the highest tumor concentration. Sections were m...

example 3

Molecular Predictors of Irinotecan Efficacy

[0192] The purpose of this study was to investigate whether mRNA levels of enzymes involved in 5-FU metabolism (TS, DPD), in CPT-11 metabolism (MDR1, Topoisomerase 1), in angiogenesis (COX-2, EGFR, IL-8, VEGF) and in DNA-repair / drug detoxification (ERCC1, GSTP1) are associated with the clinical outcome of patients with colorectal cancer (CRC) treated with first-line CPT-11 / 5-FU (CPT-11 based chemotherapy).

Patients

[0193] Fifty-four patients with histopathologically confirmed metastatic CRC, who received first-line CPT-11 / 5-FU based treatment, were included in this study of molecular markers and clinical outcome of CPT-II based therapy. Approval for this study was obtained from the Institutional Review Board of the University of Southern California, Keck School of Medicine. Written informed consent for tissue and blood collection to study molecular correlates was obtained.

[0194] All 54 patients received a first-line CPT-11 / 5-FU based ch...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Magnetic fieldaaaaaaaaaa
Fractionaaaaaaaaaa
Fractionaaaaaaaaaa
Login to view more

Abstract

The invention provides compositions and methods for determining the increased risk for recurrence of certain cancers and the likelihood of successful treatment with one or both of chemotherapy and radiation therapy. The methods comprise determining the type of genomic polymorphism present in a predetermined region of the gene of interest isolated from the subject or patient. Also provided are nucleic acid probes and kits for determining a patient's cancer risk and treatment response.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit under 35 U.S.C § 119(e) of provisional applications U.S. Ser. Nos. 60 / 585,019; 60 / 653,188 and 60 / 677,161, filed Jul. 1, 2004; Feb. 14, 2005 and May 2, 2005, respectively. The contents of these applications are incorporated by reference into the present disclosure.FIELD OF THE INVENTION [0002] This invention relates to the field of pharmacogenomics and specifically to the application of genetic polymorphism to diagnose and treat diseases. BACKGROUND OF THE INVENTION [0003] In nature, organisms of the same species usually differ from each other in some aspects, e.g., their appearance. The differences are genetically determined and are referred to as polymorphism. Genetic polymorphism is the occurrence in a population of two or more genetically determined alternative phenotypes due to different alleles. Polymorphism can be observed at the level of the whole individual (phenotype), in variant forms of pro...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C12Q1/68A61K31/7072A61K31/513A61N5/00A61K39/395
CPCA61K2039/505C07K16/2863C07K2317/24C12Q1/6886C12Q2600/106C12Q2600/118C12Q2600/156
Inventor LENZ, HEINZ-JOSEF
Owner UNIV OF SOUTHERN CALIFORNIA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap